Integrated Analyses Identify a Master MicroRNA Regulatory Network for the Mesenchymal Subtype in Serous Ovarian Cancer

Da Yang, Yan Sun, Limei Hu, Hong Zheng, Ping Ji, Chad V. Pecot, Yanrui Zhao, Sheila Reynolds, Hanyin Cheng, Rajesha Rupaimoole, David Cogdell, Matti Nykter, Russell Broaddus, Cristian Rodriguez-Aguayo, Gabriel Lopez-Berestein, Jinsong Liu, Ilya Shmulevich, Anil K. Sood, Kexin Chen, Wei Zhang

Research output: Contribution to journalArticle

229 Scopus citations

Abstract

Integrated genomic analyses revealed a miRNA-regulatory network that further defined a robust integrated mesenchymal subtype associated with poor overall survival in 459 cases of serous ovarian cancer (OvCa) from The Cancer Genome Atlas and 560 cases from independent cohorts. Eight key miRNAs, including miR-506, miR-141, and miR-200a, were predicted to regulate 89% of the targets in this network. Follow-up functional experiments illustrate that miR-506 augmented E-cadherin expression, inhibited cell migration and invasion, and prevented TGFβ-induced epithelial-mesenchymal transition by targeting SNAI2, a transcriptional repressor of E-cadherin. In human OvCa, miR-506 expression was correlated with decreased SNAI2 and VIM, elevated E-cadherin, and beneficial prognosis. Nanoparticle delivery of miR-506 in orthotopic OvCa mouse models led to E-cadherin induction and reduced tumor growth.

Original languageEnglish (US)
Pages (from-to)186-199
Number of pages14
JournalCancer Cell
Volume23
Issue number2
DOIs
StatePublished - Feb 11 2013
Externally publishedYes

    Fingerprint

ASJC Scopus subject areas

  • Oncology
  • Cell Biology
  • Cancer Research

Cite this

Yang, D., Sun, Y., Hu, L., Zheng, H., Ji, P., Pecot, C. V., Zhao, Y., Reynolds, S., Cheng, H., Rupaimoole, R., Cogdell, D., Nykter, M., Broaddus, R., Rodriguez-Aguayo, C., Lopez-Berestein, G., Liu, J., Shmulevich, I., Sood, A. K., Chen, K., & Zhang, W. (2013). Integrated Analyses Identify a Master MicroRNA Regulatory Network for the Mesenchymal Subtype in Serous Ovarian Cancer. Cancer Cell, 23(2), 186-199. https://doi.org/10.1016/j.ccr.2012.12.020